title: Effective visualization of integrated knowledge and data to enable informed decisions in drug development and translational medicine.
abstract: Integrative understanding of preclinical and clinical data is imperative to enable informed decisions and reduce the attrition rate during drug development. The volume and variety of data generated during drug development have increased tremendously. A new information model and visualization tool was developed to effectively utilize all available data and current knowledge. The Knowledge Plot integrates preclinical, clinical, efficacy and safety data by adding two concepts: knowledge from the different disciplines and protein binding.Internal and public available data were gathered and processed to allow flexible and interactive visualizations. The exposure was expressed as the unbound concentration of the compound and the treatment effect was normalized and scaled by including expert opinion on what a biologically meaningful treatment effect would be.The Knowledge Plot has been applied both retrospectively and prospectively in project teams in a number of different therapeutic areas, resulting in closer collaboration between multiple disciplines discussing both preclinical and clinical data. The Plot allows head to head comparisons of compounds and was used to support Candidate Drug selections and differentiation from comparators and competitors, back translation of clinical data, understanding the predictability of preclinical models and assays, reviewing drift in primary endpoints over the years, and evaluate or benchmark compounds in due diligence comparing multiple attributes.The Knowledge Plot concept allows flexible integration and visualization of relevant data for interpretation in order to enable scientific and informed decision-making in various stages of drug development. The concept can be used for communication, decision-making, knowledge management, and as a forward and back translational tool, that will result in an improved understanding of the competitive edge for a particular project or disease area portfolio. In addition, it also builds up a knowledge and translational continuum, which in turn will reduce the attrition rate and costs of clinical development by identifying poor candidates early.
authors.affiliation: AstraZeneca, Södertälje SE-151 85, Sweden. lena.brynne@gmail.com.
authors.forename: Lena
authors.initials: L
authors.lastname: Brynne
authors.forename: Anders
authors.initials: A
authors.lastname: Bresell
authors.forename: Niclas
authors.initials: N
authors.lastname: Sjögren
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D003657:Decision Making; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D019359:Knowledge; D057170:Translational Research, Biomedical; D016896:Treatment Outcome